Microfluidic devices can be used to conduct biomedical research and create clinically useful technology. Particular types of microfluidic devices rely on the use of a magnetic field to separate small volumes of magnetic particles from a larger test sample that is mostly non-magnetic. In the separation process, tiny magnetic particles coated with targeting monomers or polymers (e.g., proteins) are used to specifically bind with targeted material such as cells, nucleic acids and proteins. This allows a wide range of targeted material to be separated from biologically complex test samples.
It is noted that the magnetic force on a magnetic particle is directly dependent on the particle size, the field strength of the magnetic field, and the field gradient of the magnetic field. An increase in particle size, field strength or field gradient would result in an increase in the magnetic force, giving rise to an increased magnetic separation efficiency.
Larger magnetic particles (1-10 μm in diameter) require relatively low magnetic field strength and field gradient for separation. However, they do not form stable colloidal suspensions easily. The large particles would sediment easily and would require continuous stirring of the test sample to prevent sedimentation. Additionally, the surface-to-volume ratio is low for larger magnetic particles compared to smaller ones. This tends to reduce the number of effective binding sites to targets, especially when the targets are present in low density. These various factors lead to low separation efficiency for larger magnetic particles.
On the other hand, smaller magnetic particles (of tens to hundreds of nanometers in diameter) do lend themselves to be synthesized with colloidal stability. However, a high magnetic field strength with a large field gradient is needed to generate sufficient magnetic force on the small magnetic particles.
Commercially available magnetic separators generate a high gradient magnetic field by presenting a matrix with steel wool or ferromagnetic balls to a magnetic field, or by the polarity and positioning of the magnets' location around a container with the test sample. One approach is described in U.S. Pat. Nos. 3,567,026, 3,676,337, 3,902,994 and 6,471,860. In this approach, a plastic column for admitting a flow of the test sample contains a matrix filled with steel wool or ferromagnetic balls of different sizes. This method has disadvantages, such as the non-specific entrapment of biological entities other than the targeted substance. The matrix is also harmful to certain sensitive cell types, and the targeted substance may become contaminated.
A second approach is described in U.S. Pat. Nos. 5,200,084, 4,663,029, 5,466,574 and 7,056,657. This approach comprises sets of 4 to 64 permanent magnets. These magnets are arranged to define a cavity that accommodates a container used for admitting a flow of the test sample. The polarity and positioning of the magnets located on opposite sides of the cavity produce flux lines that generate a high-gradient magnetic field. Although this approach has advantages over the first one using a matrix, it has a complicated structure and a very weak magnetic field at the center of the cavity.
Thus, there is a need in the industry for an improved microfluidic separation system.